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Effect of skeletal muscle Na(+) channel delivered via a cell platform on cardiac conduction and arrhythmia induction.

Circ Arrhythm Electrophysiol. 2012 Aug 1;5(4):831-40. Epub 2012 Jun 21
Gerard J J Boink 1 , Jia Lu , Helen E Driessen , Lian Duan , Eugene A Sosunov , Evgeny P Anyukhovsky , Iryna N Shlapakova , David H Lau , Tove S Rosen , Peter Danilo , Zhiheng Jia , Nazira Ozgen , Yevgeniy Bobkov , Yuanjian Guo , Peter R Brink , Yelena Kryukova , Richard B Robinson , Emilia Entcheva , Ira S Cohen , Michael R Rosen
Gerard J J Boink 1 , Jia Lu , Helen E Driessen , Lian Duan , Eugene A Sosunov , Evgeny P Anyukhovsky , Iryna N Shlapakova , David H Lau , Tove S Rosen , Peter Danilo , Zhiheng Jia , Nazira Ozgen , Yevgeniy Bobkov , Yuanjian Guo , Peter R Brink , Yelena Kryukova , Richard B Robinson , Emilia Entcheva , Ira S Cohen , Michael R Rosen
+ et al

[No authors listed]

Author information
  • 1 Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY 10032, USA.

摘要


BACKGROUND:In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel is largely inactivated, contributing to slow conduction and reentry. We have demonstrated that adenoviral delivery of the skeletal muscle Na(+) channel (SkM1) to epicardial border zones normalizes conduction and reduces induction of ventricular tachycardia/ventricular fibrillation. We now studied the impact of canine mesenchymal stem cells (cMSCs) in delivering SkM1. METHODS AND RESULTS:cMSCs were isolated and transfected with SkM1. Coculture experiments showed cMSC/SkM1 but not cMSC alone and maintained fast conduction at depolarized potentials. We studied 3 groups in the canine 7d infarct: sham, cMSC, and cMSC/SkM1. In vivo epicardial border zones electrograms were broad and fragmented in sham, narrower in cMSCs, and narrow and unfragmented in cMSC/SkM1 (P<0.05). During programmed electrical stimulation of epicardial border zones, QRS duration in cMSC/SkM1 was shorter than in cMSC and sham (P<0.05). Programmed electrical stimulation-induced ventricular tachycardia/ventricular fibrillation was equivalent in all groups (P>0.05). CONCLUSION:cMSCs provide efficient delivery of SkM1 current. The interventions performed (cMSCs or cMSC/SkM1) were neither antiarrhythmic nor proarrhythmic. Comparing outcomes with cMSC/SkM1 and viral gene delivery highlights the criticality of the delivery platform to SkM1 antiarrhythmic efficacy.